what is thrombosis?
the formation of clots.
Describe the steps of atherogenesis and atherothrombosis?
- fatty acid build up
- driven by LDL cholesterol
- fibrous tissue forms a plaque
- inflammatory process
- when inflammed plaque ruptures forming a thrombus
name 4 methods of platelet activation?
- thrombin (from coagulation)
- thromboxane (blocked by aspirin)
- collagen
- ADP
what receptor is involved in thrombin activation of platelets?
PAR1 or PAR4
what receptor is involved in thromboxane activation of platelets?
TPalpha
what receptor is involved in collagen activation of platelets?
GP VI
releases thromboxane
what receptor is involved in ADP activation of platelets?
P2Y1
what organ synthesis coagulation factors and fibrinogen?
the liver
what is the precursor for an enzyme that lyses clots?
plasminogen.
which clotting factors are involved in the extrinsic factors?
collagen
- factors 12, 11, 8, 9
which clotting factors are involved in the intrinsic pathway?
tissue factors
- factor 7
describe the platelet shape change process?
- activation causes a shape change
- smooth discoid –> spiculated + pseudopia
- increases surface area
- increases possibility of cell to cell interactions
what glycoproteins are on the surface of the platelets?
glycoprotein IIB/IIIa receptors
50,000 to 100,000
what G protein is coupled to P2Y1 - present in ADP activation of platelets?
G protein g
what G protein is coupled to P2Y12 - present in ADP activation of platelets?
G protein j
what does P2Y1 cause?
aggregation and shape change of platelets
what does P2Y12 cause?
sustains platelet activation, aggregation and granule release.
what releases ADP from a platelet causing further activation when shunted to outer surface receptors?
Dense granules
they amplify the process of platelet activation by ADP
what else causes platelet activation amplification?
when platelets bind together.
what other G protein coupled receptor amplifies the process of platelet activation?
PAR-1
which amplifies it via ADP
name 2 coenzymes in the fibrinolytic system?
tPA (tissue plasminogen activator)
PAI-1 ( plasminogen activator inhibitor-1)
what is fibrinolysis?
break down of fibrin/dissolving of clots
what enzyme cleaves fibrinogen to form fibrin?
thrombin
what breaks down fibrin into fibrin degradation products?
plasmin
what blocks tPA activation?
PAI-1 blocks tPA activation
describe the fibrinolytic system?
plasminogen –> plasmin via tPA
plasmin –> breaks fibring into fibrin degradation products.
what do platelet alpha granules do?
they mediate expression of surface P-selectin and release of inflammatory mediators.
what response and factor is driven by platelet alpha granules?
inflammatory response and coagulation factors.
what are cyclooxygenase 1&2 (COX-1 & COX-2)?
phospholipids form arachidonic acid - using enzyme phospholipase A2.
forms 2 pathways (prostaglanin and leukotrienes)
what does prostaglanin H2 do in platelets?
uses COX-1 to form prostaglandin H2.
forms thromboxane A2 (TXA2)
vasoconstriction and platelet aggregation
what does prostaglandin H2 do in endothelial cells?
uses COX-1/2 to form prostaglandin H2.
forms prostacyclin (PGI2)
anti-coagulant
what do platelets do in inflammation?
they interact with leukocytes through P-selectin from alpha granules.
P-selectin presented on surface allows bonding with monocytes (PSGL-1 receptors)
